Amino Acid-Dependent Activation of Liver Estrogen Receptor Alpha Integrates Metabolic and Reproductive Functions via IGF-1
Amino Acid-Dependent Activation of Liver Estrogen Receptor Alpha Integrates Metabolic and Reproductive Functions via IGF-1
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DOI：
10.1016/j.cmet.2011.01.002
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发表时间：
2011-02-02
期刊：
影响因子：
29
通讯作者：
Maggi, Adriana
中科院分区：
文献类型：
--
作者：
Della Torre, Sara;Rando, Gianpaolo;Maggi, Adriana
在整个进化过程中，生物体已经设计出了在长期饥饿的情况下限制生育力的策略。在哺乳动物中，肝脏在维持能量稳态的机制中起着核心作用。我们在这里证明，膳食氨基酸调节肝雌激素受体α（ERE α）的转录活性，通过mTOR依赖性机制。作为ER α激活的结果，肝脏IGF-1 mRNA和血液IGF-1增加。相反，热量限制或肝脏中ER α的选择性消融将血液IGF-1降低至不足以使子宫腔上皮细胞正确增殖和发情周期进展的水平。我们认为，肝脏作为关键调解人的精力充沛和生殖功能负责封锁的发情周期的情况下，蛋白质缺乏。我们的研究结果可能会提供新的见解，以了解选定形式的不孕症和绝经后妇女的代谢改变的原因。
Throughout evolution, organisms have devised strategies to limit fertility in case of prolonged starvation. In mammals, the liver plays a central role in the orchestration of mechanisms allowing for the maintenance of energy homeostasis. We here demonstrate that dietary amino acids regulate the transcriptional activity of hepatic estrogen receptor alpha (ERE alpha) through an mTOR-dependent mechanism. As a result of ER alpha activation, hepatic IGF-1 mRNA and blood IGF-1 are increased. Conversely, calorie restriction or selective ablation of ER alpha in the liver decrease blood IGF-1 to levels inadequate for the correct proliferation of the lumen epithelium in the uterus and the progression of the estrous cycle. We propose that the liver acts as critical mediator of energetic and reproductive functions responsible for the blockade of the estrous cycle in case of protein scarcity. Our findings may provide novel insights to understand the cause of selected forms of infertility and metabolic alterations in women after menopause.